Norepinephrine Plus Dobutamine Versus Epinephrine Alone for the Management of Septic Shock

NCT ID: NCT00148278

Last Updated: 2010-07-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 330 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-10-31
• Study Completion Date: 2005-12-31

Brief Summary

Catecholamines infusion is a major component of septic shock management. International guidelines recommend that norepinephrine should be preferred to epinephrine, though phase III trials are lacking. The present study aimed at comparing the efficacy and safety of norepinephrine plus dobutamine to that of epinephrine in adults with septic shock.

Detailed Description

The french Conference on Consensus on catecholamines use in septic shock has underlined the importance of carrying out a clinical trial to clarify the use of epinephrine, norepinephrine and dobutamine in the management of multiple organ failure associated with severe sepsis. The main objective of the study was therefore to compare the effects of the combination of dobutamine and norepinephrine to those of epinephrine alone in patients with septic shock. In this purpose, patients were randomly assigned to receive either epinephrine or norepinephrine plus dobutamine and drugs were titrated to maintain blood pressure over 70 mmHg. Main outcome was 28-day mortality.

Conditions

Septic Shock; Severe Sepsis; Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

norepinephrine plus dobutamine

Group Type: EXPERIMENTAL

norepinephrine and dobutamine

Intervention Type: DRUG

continuous infusion of norepinephrine titrated to maintain a mean arterial pressure at 70mmHg or more and dobutamine could be added as a continuous infusion when cardiac index was of less than 2.5 liters per squared meter of body surface

2

epinephrine

Group Type: ACTIVE_COMPARATOR

epinephrine plus placebo of dobutamine

Intervention Type: DRUG

epinephrine was titrated to maintain a mean arterial pressure at 70mmHg or more and placebo of dobutamine was titrated in case of a cardiac index lower than 2.5 liters per squared meters of body surface

Interventions

norepinephrine and dobutamine

continuous infusion of norepinephrine titrated to maintain a mean arterial pressure at 70mmHg or more and dobutamine could be added as a continuous infusion when cardiac index was of less than 2.5 liters per squared meter of body surface

Intervention Type: DRUG

epinephrine plus placebo of dobutamine

epinephrine was titrated to maintain a mean arterial pressure at 70mmHg or more and placebo of dobutamine was titrated in case of a cardiac index lower than 2.5 liters per squared meters of body surface

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Adults over 18 years
• Informed consent

Presenting from less than 7 days :

• One or more infectious site
• At least 2 of the following criteria: temperature > 38°C or < 36.5°C, respiratory rate > 20 breaths per min or PaCO2 < 32 mmHg or mechanical ventilation, heart rate > 90 beats/min, white blood cell count > 12,000/mm3 or < 4,000/mm3
• At least 2 of the following criteria: PaO2/FiO2 ratio <280 mmHg (if mechanical ventilation, urinary output of less than 0.5 mL/kg of body weight or < 30 mL/h at least 1 hour, plasma lactate > 2 mmol/L, platelet count < 100,000 /mm3

And presenting from at least 24 hours:

• Systolic blood pressure < 90 mmHg or mean blood pressure < 70 mmHg (for at least 30 min);
• 1000 mL fluid replacement or pulmonary capillary wedge pressure > 12 mmHg
• Dopamine infusion at 15 µg/kg/min for at least 1 hour, or epinephrine or norepinephrine in first intention

Exclusion Criteria

• Pregnant woman
• Obstructive cardiomyopathy
• Acute coronary disease
• Non infectious shock
• Care limitation
• White blood cell count < 500 /mm3

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: collaborator

University of Versailles

OTHER

Sponsor Role: lead

Responsible Party

Assistance Publique Hôpitaux de Paris

Principal Investigators

Djillali Annane, MD, PhD

Role: STUDY_DIRECTOR

Assistance Publique Hôpitaux de Paris - University of Versailles

Eric Bellissant, MD, PhD

Role: STUDY_CHAIR

CHU Rennes

Locations

Réanimation Médicale - Hôpital Louis Mourier

Colombes, , France

Réanimation Polyvalente - Hôpital de Corbeil

Corbeil, , France

Service de Réanimation Médicale - Hôpital Poincaré

Garches, , France

Réanimation Médicale - Hôpital André Mignot

Le Chesnay, , France

Réanimation Polyvalente - Hôpital Dupuytren

Limoges, , France

Réanimation Polyvalente - Hôpital Nord

Marseille, , France

Réanimation Chirurgicale - Hôpital Central

Nancy, , France

Service de Réanimation Médicale - Hôpital Central

Nancy, , France

Service d'anesthésiologie - HIA Val de Grâce

Paris, , France

Réanimation Médicale - Hôpital Saint Louis

Paris, , France

Réanimation Polyvalente - Hôpital Saint Joseph

Paris, , France

Réanimation Médicale - Hôpital Georges Pompidou

Paris, , France

Réanimation Médicale - CHI de Poissy

Poissy, , France

Réanimation - CH Victor Provo

Roubaix, , France

Réanimation Polyvalente - Institut Gustave Roussy

Villejuif, , France

Countries

France

References

Annane D, Vignon P, Renault A, Bollaert PE, Charpentier C, Martin C, Troche G, Ricard JD, Nitenberg G, Papazian L, Azoulay E, Bellissant E; CATS Study Group. Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial. Lancet. 2007 Aug 25;370(9588):676-84. doi: 10.1016/S0140-6736(07)61344-0.

Reference Type: RESULT

PMID: 17720019 (View on PubMed)

Other Identifiers

AOM97123

Identifier Type: -

Identifier Source: secondary_id

CIC0203/001

Identifier Type: -

Identifier Source: secondary_id

AFSSAPS 990931

Identifier Type: -

Identifier Source: org_study_id